DESCRIPTION (from the investigator's abstract): Retinal signals destined for the visual cortex for conscious perception must first pass through the lateral geniculate nucleus (LGN) of the thalamus. The afferent signals from the eye are not relayed unchanged to cortex; instead, they are actively gated and modified in the LGN. Cortical processing must depend critically on the nature of the signals that provide cortical input. Our long-term goal is to understand the full spectrum of action that the LGN is capable of enacting on cortically-directed signals, and thus to more fully understand the role of this important neural structure in vision. We believe that the spatial and temporal characteristics of visual signals are modulated in the LGN as a function of the behavioral condition. These studies will enable us to compare the modulation in the LGN that is controlled in the awake state by three fundamentally different projections from the brainstem and hypothalamus: the serotonergic, histaminergic, and previously-studied cholinergic system. While we and others have revealed the existence, anatomy and pharmacology of these systems, it is not clear how each system alters the visual signal that is transmitted to cortex. In vitro studies indicated that these systems share a common method of directly exciting cortically-projecting relay cells, but they have radically different effects on geniculate inhibitory cells, which critically shape important features of LGN cell physiological responses. Thus, we propose that each modulatory system will very differently sculpt the visual signals that are transmitted to cortex. In Specific Aim #1, we will determine how the histaminergic and serotonergic systems alter the visual response of geniculate neurons. In contrast to the known effects of the cholinergic system, which are primarily disinhibitory on LGN relay cells, we predict that activation of the histaminergic system, and even more so, the serotonergic system will strengthen the inhibition-dependent characteristics of the visual responses. In Specific Aim #2, we will determine how these systems combine to alter visual responses in LGN neurons, because all are active in the awake state. We will accomplish these aims by recording in vivo the responses of LGN neurons to sophisticated visual stimuli during specific neuromodulatory activation.